Characterization of the alnumycin gene cluster reveals unusual gene products for pyran ring formation and dioxan biosynthesis.
Alnumycin is closely related to the benzoisochromanequinone (BIQ) polyketides such as actinorhodin. Exceptional structural features include differences in aglycone tailoring that result in the unique alnumycin chromophore and the existence of an unusual 4-hydroxymethyl-5-hydroxy-1,3-dioxan moiety. Cloning and sequencing of the alnumycin gene cluster from Streptomyces sp. CM020 revealed expected biosynthesis genes for polyketide assembly, but several genes encoding subsequent tailoring enzymes were highly atypical. Heterologous expression studies confirmed that all of the genes required for alnumycin biosynthesis resided within the sequenced clone. Inactivation of genes aln4 and aln5 showed that the mechanism of pyran ring formation differs from actinorhodin and granaticin pathways. Further inactivation studies identified two genes, alnA and alnB, involved in the synthesis and attachment of the dioxan moiety, and resulted in the production of the polyketide prealnumycin.
Oja
Terhi
T
Department of Biochemistry and Food Chemistry, University of Turku, FIN-20014 Turku, Finland.
Palmu
Kaisa
K
Lehmussola
Hanna
H
Leppäranta
Outi
O
Hännikäinen
Kati
K
Niemi
Jarmo
J
Mäntsälä
Pekka
P
Metsä-Ketelä
Mikko
M
D003001:Cloning, Molecular; D004146:Dioxanes / Q000737:chemistry* / Q000378:metabolism*; D015870:Gene Expression; D016681:Genome, Fungal / Q000235:genetics; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D005810:Multigene Family / Q000235:genetics*; D009285:Naphthoquinones / Q000737:chemistry* / Q000378:metabolism*; D011714:Pyrans / Q000737:chemistry* / Q000378:metabolism*; D013302:Streptomyces / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D004146:Dioxanes; D018942:Macrolides; D009285:Naphthoquinones; D011714:Pyrans; C112189:alnumycin; C025223:1,4-dioxane